男性迟发性性腺功能减退症（LOH）严重影响老年男性健康，常规药物疗法存在副作用大等缺陷。睾丸间质细胞（LCs）数量减少是LOH核心发病机制。我们前期研究发现小分子化合物SAG可促进老年LOH小鼠睾丸间质干细胞（SLCs）向LCs分化。但SAG促进SLCs分化的机制尚未阐明。已知SAG可激活GLI1转录，类固醇生成因子（SF1）表达是SLCs分化为LCs的关键步骤。我们预实验提示GLI1可直接上调SF1转录。本项目拟进一步通过GLI1基因敲除和过表达实验、睾丸内注射SAG治疗LOH小鼠等实验，旨在获得GLI1调控SF1表达的可靠证据，揭示SAG通过GLI1调控SF1表达是SAG促进SLCs分化为LCs的分子机制，并阐明SAG治疗LOH的有效性和安全性，揭示SAG促进内源性SLCs分化为LCs是睾丸内注射SAG治疗LOH的治疗机制，为SAG治疗LOH的新疗法提供科学依据和奠定实验室基础。

The Late-onset Hypogonadism in males (LOH) seriously affects the health of old men, and there is a large side effect in conventional drug therapy. The decrease in the number of Leydig cells (LCs) is the core mechanism of LOH. In our previous study, we found that small molecule compound SAG could promote the differentiation of Stem Leydig cells (SLCs) to LCs in old LOH mice. However, the mechanism of SAG to promote the differentiation of SLCs has not been elucidated. It is known that SAG activates GLI1 transcription, and the expression of steroid generating factor (SF1) is a key step in the differentiation of SLCs into LCs. Our pre experiment suggests that GLI1 can directly regulate SF1 transcription. This project proposed by GLI1 gene knockout and overexpression experiments, intratestis injection SAG treatment of LOH mice, in order to obtain reliable evidences of GLI1 regulating SF1 expression, revealed that SAG regulates the expression of SF1 is the molecular mechanism of SAG promote the differentiation of SLCs into LCs, and expounds the safety and efficacy of SAG treatment of LOH, reveals SAG promote the differentiation of endogenous SLCs to LCs is the treatment mechanism of intratesticular injection of SAG in the treatment of LOH, to provide the scientific basis and lay the foundation of the new therapy for SAG treating LOH.